University of Colorado School of Medicine, Medical Scientist Training Program, Aurora, CO 80045, USA.
Expert Opin Investig Drugs. 2012 May;21(5):637-55. doi: 10.1517/13543784.2012.677432.
Mutations in Janus kinase 2 (JAK2), and in particular JAK2 V617F, are common in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). In the past several years, JAK2 inhibitors have been rapidly developed as targeted therapies for MPNs.
JAK2 mutations, including JAK2 V617F and unique fusion proteins, are critical for oncogenesis of some hematologic malignancies. Although JAK2 mutations are extremely rare in solid cancers, pathophysiological JAK2/STAT signaling can still promote tumor cell growth, proliferation, migration, invasion and angiogenesis. JAK2 inhibition can curtail malignant cellular behaviors and thus may be a promising therapeutic strategy.
The involvement of oncogenic JAK2 mutations in hematologic malignancies indicates that JAK2 inhibition has the potential to be a highly successful treatment option. The exact role of JAK2 signaling in solid cancers is unclear, but JAK2 inhibition may prevent disease progression by restricting malignant cell phenotypes. JAK2 inhibitors in development for the treatment of MPNs have demonstrated clinical activity with minimal toxicity. This class of agents should be investigated more rigorously for the treatment of other malignancies with aberrant JAK2 signaling with or without JAK2 mutations.
Janus 激酶 2（JAK2）突变，尤其是 JAK2 V617F，在费城染色体阴性骨髓增殖性肿瘤（MPN）中很常见。在过去的几年中，JAK2 抑制剂作为 MPN 的靶向治疗药物迅速得到发展。
JAK2 突变，包括 JAK2 V617F 和独特的融合蛋白，对某些血液恶性肿瘤的发生至关重要。尽管 JAK2 突变在实体瘤中极为罕见，但生理 JAK2/STAT 信号仍可促进肿瘤细胞生长、增殖、迁移、侵袭和血管生成。JAK2 抑制可遏制恶性细胞行为，因此可能是一种很有前途的治疗策略。
致瘤性 JAK2 突变在血液恶性肿瘤中的参与表明 JAK2 抑制具有成为高度成功治疗选择的潜力。JAK2 信号在实体瘤中的确切作用尚不清楚，但 JAK2 抑制可能通过限制恶性细胞表型来阻止疾病进展。开发用于治疗 MPN 的 JAK2 抑制剂具有最小毒性的临床活性。应更严格地研究这一类药物，以治疗伴有或不伴有 JAK2 突变的其他具有异常 JAK2 信号的恶性肿瘤。
